After entering a human body, a drug nano-carrier is diluted by a great amount of body fluid, and thus becomes less stable. In order to increase stability, the carrier is subjected to hydrophilic shell crosslinking, hydrophobic core crosslinking or core-shell interface crosslinking, so as to reduce carrier dissociation caused by dilution. However, these traditional crosslinking manners also reduce the efficiency of drug release while stabilizing the carrier. Furthermore, a very small number of crosslinking structures are biocompatible and biodegradable. This greatly limits application of these carriers in the field of biological medicine.
Complex protein components in blood easily react with carriers carrying positive charges or active groups in the carriers to make the carriers gathered and removed out of the body. Carriers smoothly entering targeted parts reduce uptake of drug carriers by cells due to cell membrane rejection, thereby influencing the bioavailability of drugs. Recently, researchers apply a charge transfer caused by acid-sensitive bond breakage to drug carriers, such that the carriers are negatively charged during body circulation, thereby effectively avoiding interaction with proteins in blood; and when entering tumor tissues, the carriers are positively charged in a weak acid environment, so that interaction between the carriers and cancer cells can be enhanced, thereby improving uptake of carriers by cells. The charge transfer is advantageous in endowing the carriers with anti-protein adsorption performance and increasing cell uptake capability.
At present, there are few reports about reversible core-crosslinked drug carriers with reversible charges, reactions needed for providing charge reversal properties and crosslinking structures are complex, and most of formed materials cannot meet biodegradability, thereby reducing the application feasibility of such materials.